Synthesis And Biological Activities Of N-Heterocycles And Triazolyl Substituted Chroman Compounds

Over the last few decades,isocyanides has been widely exploited both in organic and medicinal chemistry and in polymer science.The unique features of the isocyano group make isocyanides particularly useful for the synthesis of a number of important classes of nitrogen heterocycles.Ugi reaction has gained great attention in organic chemistry due to its high versatility,exceptional efficiency,high atom economy,and convenient one-pot operation.In this dissertation,some novel heterocycles were constructed via the isocyanide-bases reaction and post-Ugi reaction.At the same time,the new 3-triazolyl substituted chroman derivatives were synthesized using intramolecular O-arylation reaction,and their pesticide activity was studied.Some compounds had notable fungicidal activity.The details are listed below:1.The recent progress on Ugi reation,intramolecular cyclization between alkynes and nitrogen atom and their synthetic applications in heterocycles compounds was summarized.Meanwhile,a brief overview of the triazole pesticide was given.2.A novel and straightforward approach to 3,4-dihydroquinazoline-4-ols derivatives via a tandem nucleophilic addition and isocyanide cyclization was developed.The mild reaction conditions and easily accessible starting material made this method a valuable tool for generating 3,4-dihydroquinazoline-4-ols,which are of considerable interest as potential biologically active compounds or intermediates for preparing other 4-substituted 3,4-dihydroquinazolines.3,4-Dihydroquinazoline-4-ols Ⅱ-11 were confirmed by X-ray crytal analysis,NMR spectra and mass spectrometry.In order to determine their potential as lead compounds,compounds Ⅱ-11 were screened on plate-based fungicide,herbicide and insecticide assays.The results indicated that compounds Ⅱ-11 were very weak or inactive in the first-tier screening.3.We have developed a one pot synthesis of diverse imidazo[2,1-b]quinazolin-5(1H)-ones via a tandem Pd-catalysed procedure.The reactions proceed with high efficiency through Pd-catalysed cross-coupling,carbodiimide-mediated cyclization,and reogioselective 5-exo-dig intramolecular cyclization reaction.Due to the broad substituent scopes,readily available starting materials and simple one-pot operation,this new synthetic approach has the potential in synthesis of various imidazo[2,1-b]quinazolin-5(1H)-ones.Imidazo[2,1-b]quinazolin-5(1H)-ones Ⅲ-5 were confirmed by NMR spectra and mass spectrometry.In order to determine their potential as lead compounds,compounds Ⅲ-5 were screened on plate-based fungicide,herbicide and insecticide assays.The results indicated that compounds Ⅲ-5q and Ⅲ-5t showed 55%and 62%antifungal activity in the Zymoseptoria tritici(minimal media)assay at 20 ppm.compounds Ⅲ-5b and Ⅲ-5f showed 55%and 50%antifungal activity in the Uromyces viciae-fabae assay at 100 ppm.compounds Ⅲ-5a,Ⅲ-5b,Ⅲ-5c and Ⅲ-5d exhibited 90%,90%,70%and 60%herbicidal activities in the Arabidopsis thaliana assay at 10 ppm.compounds Ⅲ-5c and Ⅲ-5r exhibited 50%and 60%herbicidal activities in the Digitaria sanguinalis assay at 32 ppm.4.A novel and efficient method for preparation of polysubstituted pyrroles derivatives via sequential Ugi/Ag-catalyed cycloisomerization reaction of Ugi adduct was developed.This protocol featureed broad substrate scope and provided a novel synthetic strategy for the construction of polysubstituted pyrroles,which would be of great importance for drug discovery in terms of the structure diversity of pyrroles derivatives.3-Acylpyrroles Ⅳ-6 and pyrroles Ⅳ-7’ were confirmed by NMR spectra and mass spectrometry.In order to determine their potential as lead compounds,compounds Ⅳ-6 and Ⅳ-7’ were screened on plate-based fungicide,herbicide and insecticide assays.The results indicated that compounds Ⅳ-7’a showed 72%antifungal activity in the Uromyces viciae-fabae assay at 100 ppm.compounds Ⅳ-6c,Ⅳ-6h,Ⅳ-6i,Ⅳ-6j,Ⅳ-6o and Ⅳ-6p exhibited 86%,86%,93%,100%,86%and 86%insecticidal activity in the Plutella xylostella assay at 500 ppm.5.We have developed an unprecedented sulfur ylide participating domino cyclization reaction to construct the dibenzo[b,e]azepin-6(11H)-ones via Ugi-4CR/cyclization/unexpected rearrangement sequence,starting from easily accessible sulfunion salts,2-aminophenyl ketones,aldehydes,isocyanides in the presence of DBU.The struction of dibenzo[b,e]azepin-6(11H)-ones V-7 was confirmed by X-ray crytal analysis,NMR spectra and mass spectrometry.In order to determine their potential as lead compounds,compounds V-7 were screened on plate-based fungicide,herbicide and insecticide assays.The results indicated that compounds Ⅴ-7i,Ⅴ-7j and Ⅴ-7l exhibited potent antifungal activity in the first-tier screening.6.We have designed and synthesized a series of 3-triazolyl substituted chroman derivatives by NBS bromination,nucleophilic,hydrogenation and intramolecular O-arylation reaction.3-triazolyl substituted chromans VI-6 were confirmed by NMR spectra and mass spectrometry.In order to determine their potential as lead compounds,compounds VI-6 were screened on plate-based fungicide assays.The experimental results showed that VI-6b,VI-6k and VI-6m exhibited comparable or higher antifungal activity as compared to triadimefon in the Penicilium digitatum assay.The compounds VI-6h showed higher activity as compared to triadimefon against Magnaporthe Grisea.Some compounds exhibited potent herbicidal activities.These compounds are presented as potent fungicidal leads with novel skeletons and have potential as novel pesticide precursor compounds.